2024
Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma
El Zarif T, Semaan K, Eid M, Seo J, Garinet S, Davidsohn M, Sahgal P, Fortunato B, Canniff J, Nassar A, Abou Alaiwi S, Bakouny Z, Lakshminarayanan G, Savignano H, Lyons K, Matar S, Ali A, Saad E, Saliby R, Cordeiro P, Zhang Z, El Ahmar N, Laimon Y, Labaki C, Shah V, Freeman D, O'Toole J, Lee G, Hwang J, Pomerantz M, Signoretti S, Van Allen E, Xie W, Berchuck J, Viswanathan S, Braun D, Choueiri T, Freedman M, Baca S. Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma. Cell Reports 2024, 43: 114350. PMID: 38870013, DOI: 10.1016/j.celrep.2024.114350.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaSarcomatoid differentiationCell carcinomaResponse to immune checkpoint inhibitorsGene regulatory programsAssociated with poor survivalTreatment of renal cell carcinomaLow diagnostic yieldRandomized clinical trialsCheckpoint inhibitorsTumor histologyEpigenomic signaturesTranscription factor FOSL1Healthy volunteersPatient plasmaPoor survivalLiquid biopsyFOSL1 expressionClinical trialsProfiling histone modificationsDiagnostic approachImprove outcomesRegulatory programsPlasma samplesIntratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial.
Matar S, Jegede O, Denize T, Ghandour F, Nabil Laimon Y, El Ahmar N, Bagheri Sheshdeh A, Savla V, Mohanna R, Catalano P, Braun D, Sun M, Gupta S, Vemula S, Freeman G, Motzer R, Atkins M, McDermott D, CHOUEIRI T, Signoretti S. Intratumoral T-cell infiltration and response to nivolumab plus ipilimumab in patients with metastatic clear cell renal cell carcinoma from the CheckMate-214 trial. Journal Of Clinical Oncology 2024, 42: 4536-4536. DOI: 10.1200/jco.2024.42.16_suppl.4536.Peer-Reviewed Original ResearchProgression-free survivalAssociated with progression-free survivalMultiplex immunofluorescenceClinical trialsClinical outcomesMetastatic clear cell renal cell carcinomaIntratumoral T cell infiltrationTreated with nivolumab monotherapyMetastatic clear cell RCCClear cell renal cell carcinomaResponse to nivolumabT cell infiltrationCell renal cell carcinomaPoor-risk patientsRenal cell carcinomaClear cell RCCFormalin fixed paraffinContinuous variablesNivolumab monotherapyCox proportional hazardsAntigen-experiencedCell RCCCell carcinomaLogistic regression modelsPositive association
2023
A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma
McKay R, Leucht K, Xie W, Jegede O, Braun D, Atkins M, Grimm M, Choueiri T. A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma. The Oncologist 2023, 29: 324-331. PMID: 37950901, PMCID: PMC10994246, DOI: 10.1093/oncolo/oyad298.Peer-Reviewed Original ResearchObjective response rateClear cell renal cell carcinomaRenal cell carcinomaProgression-free survivalCell renal cell carcinomaAdvanced clear cell renal cell carcinomaOverall survivalCell carcinomaPooled analysisSix-month progression-free survivalBest objective response rateActivity of nivolumabInitiation of nivolumabNivolumab/ipilimumabPoor-risk diseasePhase II trialEligible patientsII trialObjective responsePrior immunotherapyImproved survivalRisk diseaseClinical trialsIpilimumabNivolumab
2020
Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma
Braun DA, Hou Y, Bakouny Z, Ficial M, Sant’ Angelo M, Forman J, Ross-Macdonald P, Berger AC, Jegede OA, Elagina L, Steinharter J, Sun M, Wind-Rotolo M, Pignon JC, Cherniack AD, Lichtenstein L, Neuberg D, Catalano P, Freeman GJ, Sharpe AH, McDermott DF, Van Allen EM, Signoretti S, Wu CJ, Shukla SA, Choueiri TK. Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nature Medicine 2020, 26: 909-918. PMID: 32472114, PMCID: PMC7499153, DOI: 10.1038/s41591-020-0839-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigen PresentationAntineoplastic Agents, ImmunologicalCarcinoma, Renal CellCD8-Positive T-LymphocytesChromosome DeletionChromosomes, Human, Pair 6Chromosomes, Human, Pair 9Class I Phosphatidylinositol 3-KinasesDNA-Binding ProteinsExome SequencingFemaleFluorescent Antibody TechniqueGene DeletionGenomicsHistocompatibility Antigens Class IIHistone DemethylasesHistone-Lysine N-MethyltransferaseHumansKidney NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedMutationNivolumabPrognosisProteasome Endopeptidase ComplexPTEN PhosphohydrolaseSequence Analysis, RNATOR Serine-Threonine KinasesTranscription FactorsTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsUbiquitin ThiolesteraseVon Hippel-Lindau Tumor Suppressor ProteinConceptsAdvanced clear cell renal cell carcinomaClear cell renal cell carcinomaPD-1 blockadeCell renal cell carcinomaRenal cell carcinomaCell carcinomaDegree of CD8Numerous chromosomal alterationsProspective clinical trialsSomatic alterationsInfiltrated tumorsClinical responseCell infiltrationTherapeutic responseClinical trialsTherapeutic efficacyBlockadeCcRCC tumorsTumorsPBRM1 mutationsModulates responseCD8Chromosomal alterationsImmunofluorescence analysisCarcinoma
2018
Acquired mechanisms of immune escape in cancer following immunotherapy
Iorgulescu J, Braun D, Oliveira G, Keskin D, Wu C. Acquired mechanisms of immune escape in cancer following immunotherapy. Genome Medicine 2018, 10: 87. PMID: 30466478, PMCID: PMC6249768, DOI: 10.1186/s13073-018-0598-2.Peer-Reviewed Original Research